tbuckley/cabot-search huggingface dataset:
Salvage lenvatinib/everolimus (LE) combination therapy after immune checkpoint inhibitor (ICI) and VEGFR tyrosine kinase inhibitor (TKI) for metastatic renal cell carcinoma (mRCC).
Authors: Adam Khorasanchi, Christopher Kwok, Sarah P. Psutka, Megan Hinkley, Shawn Dason, Yuanquan (Aaron) Yang, Claire F. Verschraegen, Evan Gross, Delaney Orcutt, Ming Yin
Journal: Journal of Clinical Oncology (2023)

e16520 Background: The optimal treatment for mRCC patients (pts) who have progressed after both ICI and TKI remains uncertain. LE is frequently used as a salvage treatment due to different antitumor mechanisms, but efficacy and toxicity data in this setting are limited. Methods: We retrospectively reviewed charts from two academic centers for 71 adult mRCC pts who received LE after prior ICI and TKI exposure. Collected data included patient demographics, histology, International mRCC Database Consortium (IMDC) risk group, treatment history, and toxicity details using CTCAEv5. Outcomes were objective response rate (ORR) per RECIST 1.1, median time to treatment failure (mTTF), and toxicity. Descriptive statistics, Cox proportional hazards model and Kaplan-Meier method were utilized. Results: The median age was 64 (range: 31–84). Most pts had clear cell histology (84.5%) and had undergone nephrectomy (75%). IMDC risks were favorable (19.7%), intermediate (int) (66.2%), poor (11.3%), and unknown (2.8%). Pts received a median of 3 (range 1-10) prior therapy lines (L) and 42 pts had sequential ICI and TKI, while 29 received ICI/TKI combination therapy. Average ORR was 26.8%, but numerically better when given earlier (2L/3L vs. ≥4L: 28.6% vs. 22%). The mTTF was 5.5 months (m) (95% confidence interval [CI], 3.5–7.6 m), which was not significantly changed by sequential or combinational ICI/TKI treatment exposure. In multivariable Cox analyses, int/poor IMDC risk was associated with a significantly worse TTF compared to favorable risk (HR, 2.2, 95% CI, 1.1-4.1; mTTF: 4.5 vs 12.9 m), and so was ≥4L treatment compared to 2L/3L treatment (HR, 3.2, 95% CI, 1.3-7.6; mTTF: 4.5 vs. 6.6 m). In 57 pts with int/poor IMDC risk, ≥4L treatment was associated with a significantly worse TTF (HR, 2.3, 95% CI, 1.2-4.5; mTTF: 3.6 vs. 6.6 m), while prior nephrectomy was associated with a significantly better TTF (HR, 0.46, 95% CI, 0.22-0.97; mTTF: 5.4 vs. 3.1 m) compared to those without nephrectomy. Of the 71 pts, 64% had ≥ grade 3 adverse events, 60% had treatment interruption, 44.3% had dose reduction, and 21% stopped treatment due to intolerance. Conclusions: LE therapy is feasible but has modest efficacy following ICI/TKI treatment. Pts with favorable risk, prior nephrectomy or early salvage may have a better treatment response. These observations need to be confirmed in prospective studies.
Gaps in care planning and delivery for patients with liver cancer: Baseline assessment for implementation of 4R Oncology model.
Authors: George Therapondos, Julia R. Trosman, Lingling Du, Jonathan Mizrahi, Tyler Allan Sandow, Ari Cohen, Juan Gimenez, Carol Palmer, Amanda Medina, Michelle O'Brien, Amie Tan, Christine B. Weldon
Journal: Journal of Clinical Oncology (2023)

e16136 Background: Liver cancer is a complex disease, requiring detailed care planning, patient engagement and delivery of comprehensive care, including supportive and health maintenance care. The 4R Oncology Model for patient facing care planning, patient self-management and team based delivery of complex care has the potential to address these needs. 4R (Right Info/Care/Patient/Time) significantly improves patient self-management and optimizes delivery of supportive and health maintenance care in breast and lung cancer (Trosman JCOOP 2021; Liu JCOOP 2022). The impact of 4R in liver cancer has not been examined. Ochsner Health’s multi-disciplinary live cancer team is implementing and evaluating 4R. Here we describe the baseline assessment of provider practices and patient experience of care planning and delivery of supportive and health maintenance care. Methods: Surveys of providers and patients on current care planning and delivery in liver cancer were conducted Oct 2022 – Jan 2023. We used 3 metrics of care planning and 3 metrics of care delivery (Table). Results: Survey response rates: providers 55% (33/60), patients 43% (27/63). Providers included physicians, advance practitioners, nurses and navigators from Hepatology, Transplant, Interventional Radiology and Medical Oncology. Patients were 56% female, 63% white, 37% black, 56% &lt; 30k income. In care planning, patient experience was reported at a similar rate as provider practices for informed on goal of care, but significantly higher than providers for informed on next steps in care and receiving a detailed care plan (Table). In care delivery, patient experience and provider referral practices for social and supportive care were similarly low. Rates of patients’ receiving primary care and substance abuse assistance were significantly higher than respective rates of provider referrals. Among providers, 73% give patients a verbal care plan and 27% a hand written plan. The current process to create care plans is satisfactory to 54% of providers. Conclusions: We found substantial gaps in care planning and referrals to supportive and health maintenance care. Higher rates of patients reporting receipt of care planning and services suggest that many patients may resort to their own devices in these aspects of care. Ochsner Health aims to address these gaps by implementing the 4R Oncology model in liver cancer and will share results when available. [Table: see text]
Tumor agnostic efficacy and safety of erdafitinib (erda) in patients (pts) with advanced solid tumors with prespecified <i>FGFR</i> alterations (<i>FGFRalt</i>): RAGNAR primary analysis.
Authors: Shubham Pant, Martin H. Schuler, Gopa Iyer, Olaf Witt, Toshihiko Doi, Shukui Qin, Josep Tabernero, David A. Reardon, Christophe Massard, Liam Welsh, Iwona A. Lugowska, Omar Carranza, Kim Stuyckens, Huimin Liao, Saltanat Najmi, Constance Hammond, Shibu Thomas, Spyros Triantos, Hussein Sweiti, Yohann Loriot
Journal: Journal of Clinical Oncology (2023)

3121 Background: FGFRalt are present across malignancies at various frequencies and may act as oncogenic drivers across tissue histology. Erda is an oral selective pan-FGFR tyrosine kinase inhibitor with activity and safety in pts with prespecified FGFR-altered locally advanced or metastatic urothelial carcinoma (UC) and cholangiocarcinoma . RAGNAR (NCT04083976) is an ongoing phase 2 open-label, single-arm tumor agnostic trial of erda in pretreated adult and pediatric pts with FGFRalt advanced solid tumors. Interim results showed erda clinical benefit, with an objective response rate (ORR) of 29.2%. Here we report results of the primary analysis. Methods: Pts aged ≥12 y with advanced or metastatic (non-UC) tumors of any histology with predefined FGFR1-4alt (mutations/fusions per local/central test), disease progression on ≥1 prior line of systemic therapy (tx), and no alternative standard tx received oral erda until disease progression or intolerable toxicity. The primary end point was ORR by independent review committee (IRC). Secondary end points included duration of response (DOR), disease control rate (DCR [CR + PR + SD]), clinical benefit rate (CBR [CR + PR + SD &gt;4 mo]), progression-free survival (PFS), overall survival (OS), and treatment-emergent adverse events (TEAEs). Results: At data cutoff, 217 pts were treated, median age was 57.0 y (range, 12-79), median prior systemic tx was 2 (46%; ≥3 lines of tx) with an ORR to last line prior to study entry of 10.1%. ORR to erda tx by IRC was 29.5% (95% CI, 23.5-36.0) with 6 CRs (2.8%) and 58 PRs (26.7%) in 16 distinct tumor types, including advanced CNS, thoracic, gastrointestinal, gynecologic, and rare tumors. ORR was comparable across FGFR1-3 mutations (25.3% [95% CI, 16.0-36.7]) and fusions (32.6% [95% CI, 25.1-40.9]). Median DOR, PFS, and OS were 6.9 mo (95% CI, 4.4-7.1), 4.2 mo (95% CI, 4.1-5.5), and 10.7 mo (95% CI, 8.7-12.1), respectively; DCR was 73.7% and CBR was 45.6%. 99.5% of pts experienced TEAEs, including 70.0% with grade ≥3. Treatment-related serious AEs occurred in 8.3% of pts with no treatment-related deaths. Conclusions: Primary analysis results from RAGNAR, the largest tumor agnostic trial of targeted tx to date, confirm efficacy of erda in heavily pretreated pts with FGFRalt advanced solid tumors. Erda activity was observed in adults and adolescents across tumor types, and across FGFR1-3 gene mutations and fusions. Erda tolerability was consistent with its known safety profile. Clinical trial information: NCT04083976 . [Table: see text]
Regional hyperthermia with cisplatin added to gemcitabine versus gemcitabine in patients with resected pancreatic ductal adenocarcinoma: The HEAT randomized clinical trial.
Authors: Rolf D. Issels
Journal: Journal of Clinical Oncology (2023)

e16316 Background: Regional hyperthermia (RHT) with cisplatin added to gemcitabine showed efficacy in gemcitabine-pre-treated patients with advanced pancreatic ductal adeno- carcinoma. We conducted a randomised clinical trial to investigate RHT with cisplatin added to gemcitabine (GPH) compared with gemcitabine (G) in the adjuvant setting of resected pancreatic ductal adenocarcinoma. Methods: This randomised, multicentre, open-label trial randomly assigned patients to either GPH (gemcitabine 1000 mg/m2 on day 1, 15 and cisplatin 25 mg/m2 with RHT on day 2, 3 and 15,16) or to G (gemcitabine 1000 mg/m2 on day 1,8,15), four-weekly over six cycles. Disease- free survival (DFS) was the primary end-point. Secondary end-points included overall survival (OS) and safety. Results: A total of 117 eligible patients (median age, 63 years) were randomly allocated to treatment (57 GPH; 60 G). With a follow-up time of 56.6 months, the median DFS was 12.7 compared to 11.2 months for GPH and G, respectively (p= 0.39). Median post- recurrence survival was significantly prolonged in the GPH-group (15.3 versus 9.8 months; p= 0.031). Median OS reached 33.2 versus 25.2 months (p= 0.099) with 5-year survival rates of 28.4% versus 18.7%. Excluding eight patients who received additional capecitabine in the G- arm (investigators choice), median OS favored GPH (p= 0.052). Adverse events CTCAE (Common Terminology Criteria for Adverse Events) grade &gt;=3 occurred in 61.5% (GPH) versus 63.6% (G) of patients. Two patients in the G-group died because of treatment- related toxic effects. Conclusions: The randomised controlled Hyperthermia European Adjuvant Trial study failed to demonstrate a significant difference in DFS. However, it showed a difference in post- recurrence survival and a strong trend for improved OS. Regional hyperthermia (RHT) with cisplatin offers innovative treatment options in PDAC. Clinical trial information: NCT01077427 .
Comparison of two ICI-based microtubule antagonist therapies for high-risk, non-muscle-invasive bladder cancer.
Authors: Yuanjie Niu, Hailong Hu, Hong Zheng Li, Chong Shen, Zesheng An, Zhouliang Wu, Zhe Zhang, Shiwang Huang, Gangjian Zhao, Shizheng Guo, Houyuan Chen, Kaipeng Jia
Journal: Journal of Clinical Oncology (2023)

e14629 Background: Patients with highly extensive non-muscle-invasive bladder cancer (NMIBC) whose invasion area is too vast to be removed through TURBT should receive radical cystectomy in clinical practice. Clinical practice showed that nab-paclitaxel (Nab-P) or RC48-ADC (Disitamab Vedotin, DV) in combination with tislelizumab (BGB-A317, immune checkpoint inhibitor, ICI) had good effects on these patients with acceptable adverse events (AEs). This study was to compare the efficacy and safety of these two regimens. Methods: Retrospectively collected and analyzed data from two single-center clinical trials. Eligible patients were aged 18 years or older with unresectable NMIBC who received their first dose of Nab-P/ICI or DV/ICI between July 2020 and December 2022. The primary outcome was the pathological complete response (pCR) rate in a propensity score matching (PSM) population that was performed matching using a 1:4 ratio for the DV/ICI and Nab-P/ICI groups by propensity score. The main secondary outcome was treatment-related adverse events (trAEs), assessed in all eligible populations. Results: The eligible population was 12 for DV/ICI and 69 for the control group (Nab-P/ICI). The PSM population was 12 for DV/ICI and 48 for Nab-P/ICI. pCR was 66.7% (39.1%-86.2%) for DV/ICI and 60.4% (46.3%-72.9%) for the Nab-P/ICI group (OR: 0.76; 95% CI: 0.23–2.78; Fisher's exact test P = 0.75) in the PSM population. The most common trAE in the Nab-P/ICI group was alopecia, and the incidence was significantly lower in DV/ICI (Fisher's exact test, P &lt; 0.05). Grade 3–4 trAEs were observed at 8.70% and 8.33% in Nab-P/ICI and DV/ICI, respectively. No trAE-related deaths were reported. Conclusions: The pooled results of the two studies with the efficacy and safety data showed promising ICI-based microtubule antagonist regimens in pts with highly extensive non-muscle-invasive bladder cancer (NMIBC), and DV/ICI may be preferred by pts for the low incidence of alopecia in clinical practice.
Implications of GITR expression profile for precision immunotherapeutics.
Authors: Peter Moussa, Razelle Kurzrock, Daisuke Nishizaki, Hirotaka Miyashita, Suzanna Lee, Mina Nikanjam, Ramez Nassef Eskander, Hitendra Patel, Gregory P. Botta, Sarabjot Pabla, Mary K Nesline, Jeffrey M. Conroy, Paul DePietro, Jason K. Sicklick, Shumei Kato
Journal: Journal of Clinical Oncology (2023)

e14561 Background: Glucocorticoid-induced TNFR-related protein (GITR) is a type I transmembrane protein expressed mostly on CD25+CD4+ T-regs and upregulated on all T-cells upon activation. It serves as a T-cell co-stimulatory receptor and its role in cancer treatment is being explored. While pre-clinical data using combination therapies involving GITR agonism showed promise, early clinical trials have not shown improved outcomes to date. Methods: RNA expression levels of 397 genes in 514 patients with a variety of cancer types were assessed and analyzed at OmniSeq. Transcript levels were normalized to internal housekeeping gene profiles and ranked as percentiles using a reference population. High expression was defined as ≥ 75 th percentile, and low-moderate as &lt;75 th percentile. Univariate p-values were calculated using Welch t-test or Fischer’s exact test. Multivariate p-values were calculated using logistical regression. Results: A total of 99 patients (19.3%) had GITR high expression. Cancers with the highest proportion of GITR high expression were lung (7/20, 35%) and breast (19/49, 39%), and both these cancers showed a statistically significant association with GITR high expression on multivariate analysis (lung: OR 3.5, p = 0.04, 95% confidence interval (CI) 1.06 – 10.06 CI and breast: OR 4.59, p &lt;0.001, 95% CI: 2.11 – 9.85). 30% of lung and 30.6% of breast cancer patients had a GITR high with ligand low-moderate expression profile; these cancers had the highest proportion of patients with this profile. GITR high expression showed significant association with high RNA expression of multiple known immune checkpoint proteins (PD-1, PD-L1, CTLA4, LAG3, OX40, ICOS and CD137, but not TIM3) as well as PD-L1 IHC ≥1 on univariate analysis, but statistically significant association was only seen with PD-L1 IHC ≥1 (p = 0.007) and OX40 high expression (p = 0.001) on multivariate analysis. Conclusions: While clinical trials with GITR agonism are ongoing, our data suggests selection of certain types of malignancies depending on GITR status may be required. Moreover, there is a correlation between high GITR and high OX40 RNA expression, which could imply increased efficacy using this targeted combination. Further clinical development based on this immune-profiling is warranted. [Table: see text]
Barriers to breast cancer screening in a developing middle eastern country: A nationwide survey.
Authors: Zaid A. Abdulelah, Ahmed A. Abdulelah, Lina AlQirem, Jehad AlSamhori, Ahmad Al-Qirem, Abdel Rahman AlSamhori
Journal: Journal of Clinical Oncology (2023)

e22517 Background: Breast cancer imposes a significant global health burden not only due to being constantly ranked as the leading malignancy in females, but also due to the immense resulting morbidity and mortality. Despite the presence of screening modalities, the uptake is relatively low due to unidentified barriers in many countries and regions. The Identification of these barriers towards screening is of paramount importance to tackle the health burden imposed by breast cancer, especially in countries like Jordan, a developing middle eastern country. Methods: A self-reporting survey consisting of comprehensive questions regarding the participant’s demographics, medical history, knowledge about breast cancer and the screening modalities was distributed to females aged 25 years and above with no prior history of breast cancer who are residing across the different regions of Jordan. The first consecutive 790 participants were enrolled, and data analysis was performed to identify the key barriers. Results: The mean age of the enrolled study population was 41 ± 9 years old with the majority being married (82.8%), have underwent a higher level of education (86.5%), are non-smokers (75.2%), and are medically insured (72.4%). 209 participants (26.5%) had reported a family history of breast cancer, while 83.4% of the participants reported awareness about breast cancer screening modalities with breast self-examination being the most commonly known modality of screening in 39.2% of the participants. Only 22.4% of the participants were aware of the 3 available screening methods. The majority of the participants (57.1%) did not undergo previous screening. When the participants who did not undergo previous breast cancer screening were compared with those who did, the participants without prior screening were more likely to report the lack of knowledge towards screening modalities (27.7% vs 8.0%) (p-value &lt; 0.001), fear of the results (22.6% vs 13.9%) (p-value = 0.002), fear of pain during or after from the test (10.4% vs 5.9%) (p-value = 0.024), and feeling of embarrassment provoked by the screening test (15.7% vs 6.5%) (p-value &lt; 0.001) as key barriers. On the contrary, there was no statistically significant difference between the two groups when assessing financial aspect of screening uptake as a potential barrier (p-value = 0.860). Conclusions: Despite the considerably high percentage of participants being aware of breast cancer screening modalities, an alarmingly low rate of screening uptake was witnessed due to several barriers. The collective identification of lack of knowledge towards screening modalities and the nature of the available tests, in addition to the fear of the results and pain following the test, and feeling of embarrassment undoubtedly mandates the formulation of comprehensive awareness campaigns that effectively tackle these barriers.
Tissue cadherin 17 (CDH17): A favorable prognostic determinant of colorectal cancer using digital image analysis.
Authors: Lui Ng, Stella Sun, Wing Yu Shan, Pauline Leung, John Moon Luk, Dominic Chi-Chung Foo
Journal: Journal of Clinical Oncology (2023)

e14651 Background: Colorectal cancer (CRC) is the third most diagnosed malignancy and the second leading cause of cancer-death globally. The identification of robust prognostic markers for risk stratification of CRC would facilitate the accurate selection of high-risk patients for adjuvant therapies, hence improving patients’ survival and quality of living. Cadherin 17 (CDH17) is a validated biomarker for CRC characterized by its overexpression in tumor tissues (Zheng et al., 2021). CDH17 expression in tissue samples can be reliably detected by immunohistochemistry (IHC), which could potentially provide useful information for malignancy monitoring and prognosis. Nevertheless, the implementation of IHC in clinical settings is hindered by the lack of standardized guidelines. In this regard, the present study employed a standardized automated IHC platform and a digitalized sample scoring system to investigate CDH17 tissue expression and examine its clinical prognostic value in CRC. Methods: IHC was performed to assess CDH17 expression on paired tumor and adjacent non-tumor tissues from a cohort of 198 retrospective CRC cases, using the Lic3 antibody and an automated IHC system integrated with AI-digital imaging analysis. The M-score was generated for CDH17 membrane staining according to the formula (1 × % of weakly stained cells + 2 × % moderately stained cells + 3 × % of strongly stained cells)/6. Clinical correlation analysis with TNM, differentiation, and metastasis was determined. The prognostic value of tissue CDH17 was evaluated by Kaplan-Meier curves and Cox regression analyses on patients’ OS and RFS. Comparison of M-score and pathologist visual scoring was made to assess the validity of software-derived IHC scoring. Results: A significantly higher tissue CDH17 level was observed in CRC patients with advanced tumour staging (Early vs. Late stage, p = 0.0493; Mann-Whitney U test) and distant metastasis (p = 0.0188; Mann-Whitney U test). CRC patients with high M-score (M-Score High ; cut-off = 30) were associated with poorer OS and shorter RFS (OS, p = 0.015; RFS, p = 0.018; Log-rank test). Subgroup analysis revealed that M-Score High in early-stage CRC predicts patients’ disease recurrence of less than 2 years after curative surgery (p = 0.025; Log rank test). Multivariate cox regression analysis showed that CDH17 was an independent prognostic factor for OS (HR = 1.918, 95% CI = 1.001-3.676, p = 0.05). A comparison of software-derived CDH17 M-score with pathologist scoring demonstrated good correlation of 0.7257 (p &lt; 0.0001, n = 36; Pearson correlation). Conclusions: The present study suggests that CDH17 is a potential biomarker of poor prognosis for CRC. Quantification of tissue CDH17 level using a standardized automated IHC platform and digital image analysis could aid in patient stratification which allows efficient treatment strategies for better survival outcomes.